Intra-Portal Alone Versus Intra- and Extra-Portal Transplantation of Pancreatic Islets After Total Pancreatectomy for Chronic Pancreatitis

NCT03779139 | Completed DMC

• 1 other identifier: SURG-2017-26057
• Study Type: interventional
• Target: 23
• Locations: 1 country
• Sites: 1

Brief Summary

Randomized pilot trial of patients (n=30) undergoing Total Pancreatectomy and Islet AutoTransplant (TPIAT). Patients with islet harvest of greater than 5000 islet equivalents/kg body weight will be randomized to receive a portion of their islets into an omental pouch. For outcomes related to islet function, a group of normal volunteers (n=15) will be studied as a comparator group.

Conditions

Chronic Pancreatitis; Diabetes Mellitus; Islet Cell Transplantation

Keywords

total pancreatectomy with islet autotransplant

Outcome Measures

Primary Outcomes (11)

• Portal vein thrombosis

  Portal vein thrombosis is associated with higher tissue volume infused into the portal vein and higher portal pressures and is assessed using abdominal ultrasound.

  Post operative day 4 or 5.

• Clavien-Dindo classification of surgical complications

  Grades surgical complications based on the level of treatment necessary to treat the complication.

  Within 30 days of surgery

• Mixed Meal Tolerance Test

  Patient is given Boost HP (6cc/kg), ingested 5 minutes after t=0 blood draw. Blood is drawn every half hour for 2 hours.

  1 year

• Intravenous Glucose tolerance test

  Patients are given a bolus of 0.2mg/kg of dextrose at t=0. Blood samples will be drawn at t=-10,-5,-1,2,3,4,5,7 and 10 minutes

  1 year

• Glucose potentiated arginine stimulation

  Starting immediately after glucose tolerance test (time t=10 minutes), 20% dextrose will be infused to maintain a glucose \~230mg/dL until test is completed. Glucose levels are measured every 5 minutes to maintain glucose in the target range after 40 minutes of continuous 20% dextrose infusion, After 40 minutes of continuous D20% infusion, baseline samples for glucose, insulin, and C-peptide are drawn (three samples over 10 minutes), a bolus of 5 grams arginine is given (at time 55 minutes), and samples for glucose, insulin, and C-peptide are taken at 2, 3, 4, and 5 minutes after the arginine bolus.

  1 year

• Hypoglycemic clamp

  A stepped hypoglycemic clamp protocol with variable glucose infusion rates will be performed to achieve 45 min glucose plateaus at 70, 60, and 50 mg/dl.Glucagon responses will be calculated by subtracting the mean of the three baseline values observed prior to the clamp from glucagon levels observed at 70, 60, and 50 mg/dl glucose nadirs during the clamp

  1 year

• Continuous glucose monitoring

  3 days of CGM monitoring at one year will be obtained for mean glucose,standard deviation, and percent of time in hypo- and hyperglycemia

  1 year

• Hemoglobin A1c levels

  Measure of average glucose levels over last several weeks

  1 year

• Insulin Use

  calculated as units/kg/day, will be assessed from glucose and insulin diaries maintained by patients for 14 days, overlapping with day 90

  1 year

• Hypoglycemic episodes

  All severe hypoglycemic events will be recorded. This is defined based on American Diabetes Association criteria as a hypoglycemic episode \<54 mg/dL or (if not measured) associated with prompt recovery upon administration of glucose in which a patient is mentally or physically incapacitated and requires assistance from another person to treat the hypoglycemia.

  1 year

• Clarke score

  is determined from eight questions characterizing the participant's exposure to episodes of moderate and severe hypoglycemia; it evaluates symptomatic responses to hypoglycemia. A score of 4 or greater suggests impaired awareness of hypoglycemia

  1 year

Study Arms (3)

Intrahepatic islets alone

ACTIVE COMPARATOR

Procedure: Intrahepatic islets alone

Intrahepatic and omental pouch islets

EXPERIMENTAL

Procedure: Intrahepatic islets and islets in the omental pouch

Normal Volunteers

SHAM COMPARATOR

Other: Normal Volunteers

Interventions

Intrahepatic islets and islets in the omental pouch PROCEDURE

Patients with islet harvest of \>5000 islet equivalents per kg body weight will be randomized in a 1:1 ratio to 4000 IEq/kg delivered via intraportal route and the remainder implanted into a constructed omental pouch.

Intrahepatic and omental pouch islets

Intrahepatic islets alone PROCEDURE

This is the standard of care procedure. Patients with islet harvest of \>5000 islet equivalents per kg body weight will be randomized in a 1:1 ratio to all islets autotransplanted intrahepatically via the intraportal route.

Intrahepatic islets alone

Normal Volunteers OTHER

These individuals will undergo metabolic testing as well as islet cell function testing.

Normal Volunteers

Eligibility Criteria

• Age: 18 Years - 68 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 18-68
• Scheduled for total pancreatectomy and IAT at U of MN. All patients who are approved for pancreatectomy and IAT at U of MN are reviewed by a multi-disciplinary committee including surgeons, gastroenterologists specializing in pancreatic disease, a pain specialist psychologist, and endocrinologist to confirm the diagnosis of chronic pancreatitis and candidate suitability for surgery.
• Able to provide informed consent

You may not qualify if:

• Pre-Existing diabetes mellitus fasting blood glucose\>115mg/dl, or hemoglobin A1c level \>6.0% because these are all evidence of inadequate beta-cello mass.
• Use of any of the following treatments in the 30 days prior to enrollment: insulin, metformin, sulfonylureas, glinides, thiazolidinediones, GLP-1 agonists, DPP-4 inhibitors, or amylin.
• ALT or AST\>2.5 times the upper limit of normal (ULN). Bilirubin\>ULN, unless due to benign diagnosis such as Gilbert's.
• Any of the following hematologic abnormalities: server anemia (hemoglobin \<10 g/dL), thrombocytopenia (\<150/mm3), or neutropenia(\<1.0 x 109/L).
• Current use or expected use of oral or injected corticosteroids, or any mediation likely to affect glucose tolerance. However, use of hydrocortisone for physiologic replacement, or use of any topical, inhaled or intranasal glucocorticoid is permitted.
• Current or expected use of any other immunosuppressive agent.
• Known coagulopathy, or need for anticoagulant therapy preoperatively (coumadin, enoxaparin), or any history of pulmonary embolism.
• For females, plans to become pregnant or unwillingness to use birth control for the study duration.
• Inability to comply with the study protocol.
• Untreated psychiatric illness that may interfere with ability to give informed consent, or other developmental delay or neurocognitive disorder that impairs with a patient's ability to consent on their own behalf.
• Any other medical condition that , in the opinion of the investigator, may interfere wit the patient's ability to successfully and safely complete the trial.

Sponsors & Collaborators

• University of Minnesota: lead

Study Sites (1)

University of Minnesota

Minneapolis, Minnesota, 55455, United States

Location

MeSH Terms

Conditions

Pancreatitis, Chronic; Diabetes Mellitus

Condition Hierarchy (Ancestors)

Pancreatitis; Pancreatic Diseases; Digestive System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Study Officials

• Greg Beilman, MD

  University of Minnesota, Department of Surgery

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 5, 2018
• First Posted: December 19, 2018
• Study Start: August 1, 2019
• Primary Completion: December 31, 2024
• Study Completion: December 31, 2024
• Last Updated: January 27, 2025

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)